The long term goals of this work include the development of an understanding of the role(s) of the ser/thr protein kinase Rsk family in signal transduction within the mitogen-activated protein kinase (MAPK) pathway, and the identification of new classes of potential antitumor agents. The immediate objectives include - chemical synthesis of analogues of a group of kaempferol glycosides shown to mediate highly selective inhibition of Rsk2 - synthesis of analogues of a second class of inhibitors identified from the NCI repository by in silico screening - identification of additional naturally occurring inhibitors of p90 Rsk that have different types of chemical structures and properties This work is relevant to public health in that a potent and selective Rsk inhibitor is likely to exhibit activity useful for the treatment of certain cancers, notably breast cancer.